A variety of immunodeficiency states have been described in humans and in experimental animals with malignant disease. This project proposes to examine immunoregulatory mechanisms in human cancer, with emphasis on the role of interferons (IF). Originally defined by their antibiral activities, IFs have been shown to mediate a variety of immunoregulatory functions. Preliminary work in this laboratory has established a role for IFs in mediating the regulatory effects of human Concanavalin A-induced suppressor cells, and of suppressor cells generated by exposing lymphocytes to IF-inducers such as viruses, antigens, and tumor cells. IFs are critically involved in the regulation of natural cytotoxicity, and thus have a potentially important role in immune surveillance against tumor growth. We have found that peripheral blood leukocytes (PBL) from many cancer patients, particularly those with disseminated disease, fail to exhibit natural cytotoxicity against K562 target cells in vitro. Treatment of PBL with IF or IF-inducers prior to cytotoxicity assay corrects the defect in some but not all patients, suggesting differing sensitivity of PBL from different donors to the immunoregulatory effects of IF. The aims of this research proposal are to determine: (1) the mechanism(s) of IF-mediated suppression induced by Con A, viruses and tumor cells; (2) the nature of the defect in NK activity in cancer patients; (3) whether PBL from cancer patients are normal in their ability to produce IFs in response to various IF-inducers; (4) whether cancer patients' PBL exhibit normal sensitivity to the immunoregulatory effects of IFs; and (5) whether IFs can be induced from PBL from breast cancer patients using a partially purified breast cancer-associated antigen known to produce inhibition of leukocyte migration in the majority of breast cancer patients tested.